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ObjectiveThe association between serum uric acid (UA) and spontaneous hemorrhagic transformation (HT) has been seldom studied, and the role of UA in spontaneous HT remains unclear. This study aims to investigate the sex-dependent association between UA and spontaneous HT in patients with ischemic stroke.MethodWe retrospectively included patients with ischemic stroke in a tertiary academic hospital between December 2016 and May 2020. Patients were included if they presented within 24 h after the onset of symptoms and did not receive reperfusion therapy. Spontaneous HT was determined by an independent evaluation of neuroimaging by three trained neurologists who were blinded to clinical data. A univariate analysis was performed to identify factors related to spontaneous HT. Four logistic regression models were established to adjust each factor and assess the association between UA and spontaneous HT.ResultsA total of 769 patients were enrolled (64.6% were male patients and 3.9% had HT). After adjusting the confounders with a P < 0.05 (model A) in the univariate analysis, the ratio of UA and its interquartile range (RUI) was independently associated with spontaneous HT in male patients (OR: 1.85; 95% CI: 1.07–3.19; P = 0.028), but not in female patients (OR: 1.39; 95% CI: 0.28–6.82; P = 0.685). In models B–D, the results remain consistent with model A after the adjustment for other potential confounders.ConclusionsHigher serum UA was independently associated with a higher occurrence of spontaneous HT in male patients who were admitted within 24 h after the stroke onset without receiving reperfusion therapy.

Auxin is one of the most important plant growth regulators of plant morphogenesis and response to environmental stimuli. Although the biosynthesis pathway of auxin has been elucidated, the mechanisms regulating auxin biosynthesis remain poorly understood. The transcription of auxin biosynthetic genes is precisely regulated by complex signaling pathways. When the genes are expressed, epigenetic modifications guide mRNA synthesis and therefore determine protein production. Recent studies have shown that different epigenetic factors affect the transcription of auxin biosynthetic genes. In this review, we focus our attention on the molecular mechanisms through which epigenetic modifications regulate auxin biosynthesis.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas9 mediated gene editing systems have been used in a variety of organisms, including plants. This system can efficiently edit target genes to generate mutants, especially multiplex mutants, which are invaluable genetic materials for gene functional studies. Although the use of traditional hybridization technology to construct multiplex mutants has been widely used in plant research, the complex screening and identification, long construction cycle and other problems have always troubled researchers. Therefore, in the current plant science research, the use of CRISPR-Cas9 mediated multiplex genome editing to construct multiplex mutants has become a mainstream technology. Here, we designed an improved plant CRISPR-Cas9 mediated multiplex genome vector system. The In-fusion cloning technology was selected to conveniently assemble multiple tandem sgRNA (Single-guide RNA) expression frames. In this system, Cas9-free plants can be easily selected by examining mCherry fluorescence in T2 transgenic plants. By using this system, Cas9-free homozygous triple mutant was obtained, demonstrating the availability of our system.

Two new species belonging to the varius group of Coccophagus, C. breviclavulussp. nov. and C. perlucidussp. nov., are described from Xishuangbanna Rainforest (China, Yunnan). Coccophagus anchoroides (Huang) and C. yunnana Wang, Huang & Polaszek are recorded. A tentative key to world species of this group is provided. Partial nuclear ribosomal 28S-D2 of these four species and other six species were sequenced and subjected to a phylogenetic analysis. Phylogeny of C. varius group is discussed.

Two new species belonging to the

Substance P contributes to the pathogenesis of pain by acting on NK-1R, specialized sensory neurons that detect noxious stimuli. Aprepitant, an antagonist of NK-1R, is widely used to treat chemotherapy-induced nausea and vomiting. In this study, we used LPS-stimulated BV-2 microglia cell line and animal models of inflammatory pain to explore the analgesic effect of aprepitant on inflammatory pain and its underlying mechanism. The excitability of DRG neurons were measured using whole-cell patch-clamp recordings. The behavioral tests were measured and the morphological changes on inflamed paw sections were determined by HE staining. Changes in the expressions of cytokine were measured by using real-time quantitative PCR analysis and ELISA method. Immunofluorescence and western blotting were used to detect the microglia activation and MAPK. Aprepitant treatment significantly inhibited the excitability of DRG neurons. The pain behavior and the paw tissues inflammatory damage were significantly relived after the administration of aprepitant compared to formalin group. Aprepitant significantly suppressed the activation of microglia, phosphorylation of JNK and p38 MAPK, as well as the mRNA and protein expressions of MCP-1, TNF-α, IL-6, and IL-1β, in vivo and in vitro. The LPS-induced over-translocation into nucleus of NF-κBp65 was down-regulated following aprepitant treatment in BV-2 cells. The present study suggests that aprepitant attenuates inflammatory pain in mice via suppressing the phosphorylation of JNK and p38, and inhibiting the NF-κB signaling pathway.

SARS-CoV-2 is a positive-sense RNA virus and it is the causative agent of the global COVID-19 outbreak. COVID-19 is similar to the previous outbreaks for instance SARS in 2002-2003 and MERS in 2012. As the peptides have many advantages, peptide-based therapeutics might be one of the possible ways in the development of COVID-19 specific drugs. SARS-CoV-2 enters into a human via its S protein by attaching with human hACE2 present on the cell membrane in the lungs and intestines of humans. hACE2 cleaves S protein into the S1 subunit for viral attachment and the S2 subunit for fusion with the host cell membrane. The fusion mechanism forms a six-helical bundle (6-HB) structure which finally fuses the viral envelope with the host cell membrane. hACE2 based peptides such as SBP1 and Spikeplug have shown their potential as antiviral agents. S protein-hACE2 interaction and the SARS-CoV-2 fusion machinery play a crucial part in human viral infection. It is evident that if these interactions could be blocked successfully and efficiently, it could be the way to find the drug for COVID-19. Several peptide-based inhibitors are potent inhibitors of S protein-hACE2 interaction. Similarly, the antiviral activity of the antimicrobial peptide, lactoferrin makes it an important candidate for the COVID-19 drug development process. A candidate drug, RhACE2-APN01 based on recombinant hACE2 peptide has already entered phase II clinical trials. This review sheds light on different aspects of the feasibility of using peptide-based therapeutics as the promising therapeutic route for COVID-19.

N-terminal acetylation (NTA) is a highly abundant protein modification catalyzed by N-terminal acetyltransferases (NATs) in eukaryotes. However, the plant NATs and their biological functions have been poorly explored. Here we reveal that loss of function of CKRC3 and NBC-1, the auxiliary subunit (Naa25) and catalytic subunit (Naa20) of Arabidopsis NatB, respectively, led to defects in skotomorphogenesis and triple responses of ethylene. Proteome profiling and WB test revealed that the 1-amincyclopropane-1-carboxylate oxidase (ACO, catalyzing the last step of ethylene biosynthesis pathway) activity was significantly down-regulated in natb mutants, leading to reduced endogenous ethylene content. The defective phenotypes could be fully rescued by application of exogenous ethylene, but less by its precursor ACC. The present results reveal a previously unknown regulation mechanism at the co-translational protein level for ethylene homeostasis, in which the NatB-mediated NTA of ACOs render them an intracellular stability to maintain ethylene homeostasis for normal growth and responses. Supplementary Information The online version contains supplementary material available at 10.1186/s12870-021-03090-7.

The plant root is a dynamic system, which is able to respond promptly to external environmental stimuli by constantly adjusting its growth and development. A key component regulating this growth and development is the finely tuned cross-talk between the auxin and cytokinin phytohormones. The gradient distribution of auxin is not only important for the growth and development of roots, but also for root growth in various response. Recent studies have shed light on the molecular mechanisms of cytokinin-mediated regulation of local auxin biosynthesis/metabolism and redistribution in establishing active auxin gradients, resulting in cell division and differentiation in primary root tips. In this review, we focus our attention on the molecular mechanisms underlying the cytokinin-controlled auxin gradient in root tips.

BackgroundLumbar disc herniation (LDH) is a common condition leading to high individual, social, and economic impacts. Reported rates of spontaneous resorption of LDH vary from 35% to 100%; however, it remains unclear how spontaneous absorption, rather than re-protrusion, can be maximized.Purpose The main objective of this study was to determine the characteristics and factors enabling for spontaneous regression of extruded LDH. DesignA retrospective single center case series. Patient sampleInpatients (n = 33) with LDH who experienced spontaneous regression between September 2015 and June 2020. Outcome measuresQuestionnaire responses and magnetic resonance imaging (MRI)-determined hernia regression.MethodsA questionnaire was distributed to patients to assess factors associated with hernia resorption, the volume of herniated intervertebral discs evaluated by MRI, and the absorption ratio calculated. Multiple linear regression was used to explore factors enabling spontaneous herniated disc regression. ResultsA total of 31 patients received a mean of 5.90 conservative treatments during hospitalization, and 1.91 during rehabilitation. Of patients, 90.32% underwent bed-rest during the acute phase of the disease, and 61.29% did so during rehabilitation. Rehabilitation exercise was undertaken by 93.55% of patients, with a mean of 2.42 exercise methods per patient. Waist lumbosacral orthosis devices were worn by 80.65% of patients. Multiple linear regression showed that bed-rest days in the acute phase (X1), herniation type (X2), time wearing lumbosacral orthosis (X3), onset-treatment duration (X4), and days of bed-rest days in rehabilitation (X5) had significant effects on the spontaneous regression ratio (y) of herniated discs (all P < 0.05). The optimal linear regression equation was y = 0.616 + 0.497X1 – 0.478X2 + 0.384X3 – 0.343X4 – 0.241X5. Conclusions Our findings support that patients with extruded or sequestered LDH should receive comprehensive treatment. Early treatment, early bed-rest, and lumbosacral orthosis protection promote the spontaneous regression of herniated discs; however, bed-rest during rehabilitation is a poor prognostic factor. Adherence to rehabilitation exercise will be beneficial to the recovery of patients with LDH.

Additional file 1.

Green tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG is consumed during dieting for weight loss has not been previously reported. This study found for the first time that EGCG could induce enhanced lipid metabolism pathways, suggesting that EGCG had the so-called “fat burning” effect, although EGCG did not cause liver injury at doses of 400 or 800 mg/kg in normal mice. Intriguingly, we found that EGCG caused dose-dependent hepatotoxicity on mice under dietary restriction, suggesting the potential combination effects of dietary restriction and EGCG. The combination effect between EGCG and dietary restriction led to overactivation of linoleic acid and arachidonic acid oxidation pathways, significantly increasing the accumulation of pro-inflammatory lipid metabolites and thus mediating liver injury. We also found that the disruption of Lands’ cycle and sphingomyelin-ceramides cycle and the high expression of taurine-conjugated bile acids were important metabolomic characteristics in EGCG-induced liver injury under dietary restriction. This original discovery suggests that people should not go on a diet while consuming EGCG for weight loss; otherwise the risk of liver injury will be significantly increased. This discovery provides new evidence for understanding the “drug-host” interaction hypothesis of drug hepatotoxicity and provides experimental reference for clinical safe use of green tea-related dietary supplements.

OBJECTIVE: To investigate the incidence rate of infectious diseases during hospitalization in late preterm infants in Beijing, China, as well as the risk factors for infectious diseases and the effect of breastfeeding on the development of infectious diseases. METHODS: Related data were collected from the late preterm infants who were hospitalized in the neonatal wards of 25 hospitals in Beijing, China, from October 23, 2015 to October 30, 2017. According to the feeding pattern, they were divided into a breastfeeding group and a formula feeding group. The two groups were compared in terms of general status and incidence rate of infectious diseases. A multivariate logistic regression analysis was used to investigate the risk factors for infectious diseases. RESULTS: A total of 1 576 late preterm infants were enrolled, with 153 infants in the breastfeeding group and 1 423 in the formula feeding group. Of all infants, 484 (30.71%) experienced infectious diseases. The breastfeeding group had a significantly lower incidence rate of infectious diseases than the formula feeding group (22.88% vs 31.55%, P=0.033). The multivariate logistic regression analysis showed that breastfeeding was an independent protective factor against infectious diseases (OR=0.534, P=0.004), while male sex, premature rupture of membranes, gestational diabetes mellitus, and asphyxia were risk factors for infectious diseases (OR=1.328, 5.386, 1.535, and 2.353 respectively, P < 0.05). CONCLUSIONS: Breastfeeding can significantly reduce the incidence of infectious diseases and is a protective factor against infectious diseases in late preterm infants. Breastfeeding should therefore be actively promoted for late preterm infants during hospitalization.

CTLA-4 is an important regulator of T-cell function. Here, we report that expression of this immune-regulator in mouse B-1a cells has a critical function in maintaining self-tolerance by regulating these early-developing B cells that express a repertoire enriched for auto-reactivity. Selective deletion of CTLA-4 from B cells results in mice that spontaneously develop autoantibodies, T follicular helper (Tfh) cells and germinal centers (GCs) in the spleen, and autoimmune pathology later in life. This impaired immune homeostasis results from B-1a cell dysfunction upon loss of CTLA-4. Therefore, CTLA-4-deficient B-1a cells up-regulate epigenetic and transcriptional activation programs and show increased self-replenishment. These activated cells further internalize surface IgM, differentiate into antigen-presenting cells and, when reconstituted in normal IgH-allotype congenic recipient mice, induce GCs and Tfh cells expressing a highly selected repertoire. These findings show that CTLA-4 regulation of B-1a cells is a crucial immune-regulatory mechanism., CTLA-4 is an important co-inhibitory receptor for T cells. Here, the authors show that CTLA-4 also has a function on B-1a cells, as conditional deletion results in activation of these cells and knockout mice develop an autoimmune profile.

Objective: To investigate the clinical characteristics and treatment methods of rhabdomyosarcoma in children and the efficacy of the methods. Methods: The clinical data of 30 children with rhabdomyosarcoma who were admitted to our hospital from August 2013 to August 2017 were retrospectively analyzed. The clinical characteristics were summarized, and the curative effect and prognosis were evaluated. Results: Among all the children (N=30), there were 20 males and 10 females, with a median age of 3.5 years. As to the primary site, there were 13 cases of head and neck, 11 cases of trunk, three cases of urogenital system and three cases of limbs. There were 25 cases of embryonic type, 4 cases of alveolar type and one case of polymorphic type. As regards clinical stage, there were one case of stage I, 9 cases of stage II, 13 cases of stage III and 7 cases of stage IV. There were one case of low risk, 19 cases of medium risk and 10 cases of high risk. Eight cases received surgery alone, 22 cases received combined treatment of surgery and chemotherapy (the chemotherapeutics followed three schemes, low-risk group (VAC+VA), moderate risk group (VAC) and high risk group (alternating use of VDC and IE). Among all the cases (N=30), there were 14 cases of complete remission (CR), five cases of partial remission (PR), four cases of stable disease (SD), and 7 cases of progressive disease (PD). The CR rate was (N=14, 46.7%). The three-year overall survival (OS) rate was (N=19, 63.3%). The clinical efficacy and prognosis of children receiving surgery and chemotherapy were better than those of children receiving surgery alone, and the difference was statistically significant (P

The auxin IAA is a vital plant hormone in controlling growth and development, but our knowledge about its complicated biosynthetic pathways and molecular regulation are still limited and fragmentary. cytokinin induced root waving 2 (ckrw2) was isolated as one of the auxin-deficient mutants in a large-scale forward genetic screen aiming to find more genes functioning in auxin homeostasis and/or its regulation. Here we show that CKRW2 is identical to Histone Monoubiquitination 1 (HUB1), a gene encoding an E3 ligase required for histone H2B monoubiquitination (H2Bub1) in Arabidopsis. In addition to pleiotropic defects in growth and development, loss of CKRW2/HUB1 function also led to typical auxin-deficient phenotypes in roots, which was associated with significantly lower expression levels of several functional auxin synthetic genes, namely TRP2/TSB1, WEI7/ASB1, YUC7 and AMI1. Corresponding defects in H2Bub1 were detected in the coding regions of these genes by chromatin immunoprecipitation (ChIP) analysis, indicating the involvement of H2Bub1 in regulating auxin biosynthesis. Importantly, application of exogenous cytokinin (CK) could stimulate CKRW2/HUB1 expression, providing an epigenetic avenue for CK to regulate the auxin homeostasis. Our results reveal a previously unknown mechanism for regulating auxin biosynthesis via HUB1/2-mediated H2Bub1 at the chromatin level., Li Zhang et al. characterize ckrw2, cytokinin-induced root waving 2, as a mutant form of HUB1 in Arabidopsis, the gene required for histone H2B monoubiquitination. This study implicates the involvement of H2Bub1 in regulating auxin biosynthesis.

In this paper, the mechanical parameters of the grouting consolidation body on the rock block are studied using the Acoustic velocity test case and the revised Hoek-Brown failure criterion in underground metal mines. In light of the hidden resources in the collapsed area of the underground metal mine, the intact rock drilling core cannot be obtained to perform the mechanical test because of extreme damage or because it is completely broken. Therefore, pure cement grouting is used to reinforce the extremely broken rock mass within the collapsed area of the hidden resources. The RQD value and water permeability are tested to indicate that cement pastes can fill the cracks in broken rock blocks and can improve the integrity of the broken rock mass. To detect the grouting consolidation effect of the fractured rock mass and evaluate the mechanical parameters of the consolidation body, a nondestructive test is applied to measure the Acoustic velocity of the consolidation body after grouting. Initially, the measured Acoustic velocity is adopted to calculate the damage index (or integrity index), which is approximately equivalent to the disturbance factor. Then, the modified Hoek-Brown failure criterion is used to evaluate the mechanical parameters of the grouting consolidation body. Finally, to verify this method, the mechanical parameters of the rock mass are also obtained by a laboratory test. The outcomes show that the current research can serve as a practical method when evaluating rock mass quality by the grouting treatment.

Public Key Encryption with Keyword Search (PEKS) is a desirable technique to provide searchable functionality over encrypted data in public key settings, which allows a user to delegate a third party server to perform the search operation on encrypted data by means of keyword search trapdoor without learning about the data. However, the existing PEKS schemes cannot be directly applied to practice due to keyword guessing attack or the absence of a mechanism to limit the lifetime of a trapdoor. By addressing these issues at the same time, this paper presents a Public Key Encryption Scheme with Temporary and Fuzzy Keyword Search (PETFKS) by using a fuzzy function and an encryption tree. The proposed PETFKS scheme is proven adaptively secure concerning keyword confidentiality and backward and forward secrecy in the random oracle model under the Bilinear Di e-Hellman assumption. Moreover, it is also proven selectively secure with regard to the resistance of keyword guessing attack. Furthermore, the security and e ciency analyses of the proposed scheme are provided by comparing to the related works. The analyses indicate that the proposed scheme makes a threefold contribution to the practical application of public key encryption with keyword search, namely o ering secure search operation, limiting the lifetime of a trapdoor and enabling secure time-dependent data retrieval.

Lingling Yu,1,2 Wei Wang,1 Liang Li,2 Qingguang Qin,2 Yutian Yu,2 Kun Liu,2 Yufeng Zhao,2 Peijing Rong,2 Bing Zhu2 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; 2Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China Background: The transmission of visceral nociception can be inhibited by electroacupuncture (EA) at the spinal level. However, relationships between current intensity and EA-induced analgesia are still lacking. This study compares the effects of different intensities of EA at local acupoints and heterotopic acupoints on nociceptive responses of spinal wide dynamic range (WDR) neurons induced by noxious colorectal distension (CRD). Materials and methods: Experiments were conducted on 40 Sprague Dawley rats anesthetized with 10% urethane. Discharges of WDR neurons in the L1–L3 segments of the dorsal horn of the spinal cord were recorded extracellularly by glass micropipettes. Different intensities of EA (0.5, 1, 2, 4, 6, and 8 mA, 0.5 ms, 2 Hz) were applied to contralateral “Zusanli” (ST 36) or “Neiguan” (PC 6), with either the same or different segmental innervation of the colon. Results: In local acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 0.5–8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 0.5–4 mA, but the inhibiting rate reached a plateau when EA exceeded 4 mA. In heterotopic acupoints, the increased discharges of WDR neurons evoked by CRD were significantly inhibited by EA at 2–8 mA. A positive relationship between current intensity and the inhibiting rate was observed within 2–6 mA. Further increase in the current beyond 6 mA also resulted in a plateau effect. Conclusion: Within a certain range, the nociceptive responses of dorsal horn neurons induced by CRD could be inhibited by EA in an intensity-dependent manner. Keywords: electroacupuncture, current intensity, wide dynamic range, colorectal distension

Summary In mobility network capacity planning, characterizing the mobility network traffic is one of the most challenging tasks. Besides the growth trend and multiple periodic temporal patterns for normal traffic, the problem is complicated by the occasionally intense traffic for special events and its dynamic spatial relationships. Identifying the areas that have different traffic patterns compared with their neighbouring areas is a problem of spatial hotspot detection. In the paper, a copula-based method is proposed: using a multivariate extreme value copula, the upper tail dependence of the traffic distributions of neighbouring cell towers is evaluated, and then a cluster of multiple time series (i.e. multiple cell towers) with high upper tail dependence is detected. The method proposed is validated by using synthetic data as well as real mobility traffic data.

Host specificity of parasitoids may be measured by various specialization indices to assess the variation of interaction strength among species and the structure of the wider interaction network. However, the conclusions from analyses at the species and network levels may differ, which remains poorly explored. In addition, the recovery of cryptic species of hosts and parasitoids with molecular data may affect the structure of inferred interaction links. We quantified host specificity of hymenopteran parasitoids (family Encyrtidae) on armored scale insects (Hemiptera: Diaspididae) from a wide geographic sampling range across the Chinese Mainland based on both morphological and molecular species delimitation. Mitochondrial COI and nuclear 28S markers detected high cryptic species diversity in the encyrtids and to a lesser degree in the diaspidids, which divided generalist morphospecies into complexes of specialists and generalists. One‐to‐one reciprocal host–parasite links were increased in the molecular data set, but different quantitative species‐level indices produced contrasting estimates of specificity from various one‐to‐multiple and multiple‐to‐multiple host–parasite links. Network indices calculated from DNA‐based species, compared to morphology‐based species definitions, showed lower connectance and generality, but greater specialization and compartmentalization of the interaction network. We conclude that a high degree of cryptic species in host–parasitoid systems refines the true network structure and may cause us overestimating the stability of these interaction webs.